7,12-Dimethylbenz[a]anthracene

About: 7,12-Dimethylbenz[a]anthracene is a research topic. Over the lifetime, 1717 publications have been published within this topic receiving 40892 citations.

Quercetin suppresses cytochrome P450 mediated ROS generation and NFκB activation to inhibit the development of 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinomas

Abstract: Increased production of reactive oxygen species (ROS) has long been recognized to play a pivotal role in carcinogenesis. Quercetin, a naturally occurring dietary flavonoid is known for its ROS scavenging properties. The present study was designed to investigate the chemopreventive and chemotherapeutic effects of quercetin based on cytochrome P450 (CYP) mediated ROS generation, ROS-induced cellular damage and activation of the NFκB signalling circuit during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Administration of quercetin inhibited the development of DMBA-induced HBP carcinomas by impairing CYP-mediated ROS production via downregulation of the expression of CYP1A1 and CYP1B1, and upregulation of antioxidant defences. Attenuation of ROS generation by quercetin in turn abrogated NFκB signalling by preventing the phosphorylation and degradation of IκB, nuclear translocation of NFκB and transactivation of its target genes associated with cell proliferation and apoptosis evasion. Thus dietary flavonoids such as quercetin that can block ROS generation and inhibit the redox regulated transcription factor NFκB, by virtue of their antioxidant potential are promising candidates for future antioxidant-based anticancer regimens.

Serum Estrogens and Estrogen Responsiveness in 7,12-Dimethylbenz[a]anthracene-Induced Mammary Tumors as Influenced by Dietary Fat

Abstract: The effect of dietary fat on mammary tumor incidence, estrogen-binding capacity as related to the hormone dependency of the tumors, and circulating estrogen levels in Sprague-Dawley rats given an oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. Rats were fed diets consisting of 0.5, 5, or 20% corn oil starting at weaning and were administered 5 mg DMBA at 50 days of age. Tumor incidences were 13, 46, and 75% for the groups given 0.5, 5, and 20% fat, respectively, when the experiment was terminated 20-22 weeks later. Serum estradiol, measured at proestrus at 50 days of age and at the end of the experiment, was slightly depressed at both time points in rats fed the 0.5% fat diet but was similar in the other 2 groups. Serum estrone levels were not significantly different at either time point. Estrogen receptor levels in the tumor were the same in the groups given 5 and 20% fat but were lower in the group given 0.5% fat. No difference was detected in the progesterone receptor concentrations. Furthermore, most (approximately 70%) of the tumors in all 3 dietary groups regressed in response to ovariectomy, which suggested that dietary fat has very little influence on the estrogen dependence of the tumor. This observation suggested that fat intake does not result in any intrinsic difference in the biochemical action of estrogen.

Inhibition of 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation in mice by dehydroepiandrosterone and two synthetic analogs

Abstract: Previous work has demonstrated that the adrenal steroid, dehydroepiandrosterone (3-beta-hydroxy-5-androsten-17-one, DHEA), has broad spectrum tumor chemopreventive activity in laboratory mice and rats, inhibiting the development of spontaneous breast cancer and chemically induced tumors of the lung, colon, skin, thyroid and liver. DHEA treatment produces specific side-effects, including estrogenic and androgenic action and an increase in liver weight, which could limit its use as a cancer chemopreventive drug. It is now shown that oral administration of the synthetic steroid 16 alpha-fluoro-5-androsten-17-one, which lacks the side-effects of DHEA treatment, to CD-1 mice inhibits 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation at both the initiation and promotion stage. The synthetic steroid is more potent as an inhibitor of papilloma formation than comparably administered DHEA.

The effect of pretreatment with adrenal-protecting compounds on the metabolism of 7,12-dimethylbenz[a]anthracene and related compounds by rat-liver homogenates

Abstract: 1. 7,12-Dimethylbenz[a]anthracene is converted by rat-liver homogenates into products with the properties of the 7- and 12-hydroxymethyl derivatives, the 7,12-dihydroxymethyl derivative, the related carboxylic acids and ring-hydroxylated products such as the 8,9-dihydro-8,9-dihydroxy derivative and phenols. Ring-hydroxylated products and products arising from the further oxidation of the hydroxymethyl groups were formed when the hydroxymethyl derivatives were themselves incubated with rat-liver homogenates. 2. Pretreatment of the animal with 3-methylcholanthrene or with Sudan III, which can protect rat adrenal glands from damage by 7,12-dimethylbenz[a]anthracene or by its 7-hydroxymethyl derivative, led to an increased rate of metabolism of 7,12-dimethylbenz[a]anthracene and its hydroxymethyl derivatives. The metabolic routes mainly affected were those involving the formation of ring-hydroxylated products. 3. Pretreatment with phenobarbitone led to a small increase in the rate of metabolism of the hydrocarbon and of its hydroxymethyl derivatives, but the increase appeared mainly to involve increased metabolism of the methyl and hydroxymethyl groups. 4. Pretreatment with metyrapone increased the rate of metabolism of the hydrocarbon mainly by increasing the amounts of products resulting from hydroxylation of the methyl groups: small increases in the amounts of ring-hydroxylated products were also produced. 8. Of a number of hydrocarbons and of derivatives of 3-methylcholanthrene tested as enzyme inducers, 3-methylcholanthrene itself was the most effective.